This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Mechanisms that result in the invasive nature of primary glioblastoma and metastatic breast cancer in the brain are largely unknown. We have implicated a cell adhesion/ recognition molecule as a mechanism whereby these tumor cells stimulate their own motility through binding to their cell surface receptors. Certain glioma and breast cancer cell lines express and release this molecule into the culture media both as a large fragment and also in the form of small membrane vesicles. Their cell surfaces contain receptors which then become autocrine stimulated to promote cell motility. Stimulation of tumor cells in brain could also occur if they merely express cell surface receptors;the brain is rich in this adhesion molecule along axons, and this would be in the vicinity of the tumor cells to stimulate them. Our goal is to elucidate the mechanism of glioma and breast cancer cell motility and its contribution to local invasiveness within and metastasis to the brain. The overlying hypothesis is that glioma and breast cancer cell motility is influenced either by 1) their own adhesion molecule expression and an autocrine stimulatory mechanism that involves precise cleavage and release of vesicles or 2) a stimulatory response to exogenously presented (axonal) adhesion molecule. These mechanisms are hypothesized to influence the motility, invasiveness and metastasis in our novel chick brain tumor model. Furthermore, we hypothesize that primary glioblastoma and metastatic breast cancer cells from patient surgical samples also will utilize one or both of these mechanisms to promote their high level of motility.